Goncharova Olga, Flinner Nadine, Bein Julia, Döring Claudia, Donnadieu Emmanuel, Rikirsch Sandy, Herling Marco, Küppers Ralf, Hansmann Martin-Leo, Hartmann Sylvia
Dr. Senckenberg Institute of Pathology, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany.
Institute of Informatics/Frankfurt Institute for Advanced Studies, Goethe University, 60438 Frankfurt am Main, Germany.
Cancers (Basel). 2019 Oct 2;11(10):1484. doi: 10.3390/cancers11101484.
Anaplastic large cell lymphoma (ALCL) and classical Hodgkin lymphoma (cHL) are lymphomas that contain CD30-expressing tumor cells and have numerous pathological similarities. Whereas ALCL is usually diagnosed at an advanced stage, cHL more frequently presents with localized disease. The aim of the present study was to elucidate the mechanisms underlying the different clinical presentation of ALCL and cHL. Chemokine and chemokine receptor expression were similar in primary ALCL and cHL cases apart from the known overexpression of the chemokines CCL17 and CCL22 in the Hodgkin and Reed-Sternberg (HRS) cells of cHL. Consistent with the overexpression of these chemokines, primary cHL cases encountered a significantly denser T cell microenvironment than ALCL. Additionally to differences in the interaction with their microenvironment, cHL cell lines presented a lower and less efficient intrinsic cell motility than ALCL cell lines, as assessed by time-lapse microscopy in a collagen gel and transwell migration assays. We thus propose that the combination of impaired basal cell motility and differences in the interaction with the microenvironment hamper the dissemination of HRS cells in cHL when compared with the tumor cells of ALCL.
间变性大细胞淋巴瘤(ALCL)和经典型霍奇金淋巴瘤(cHL)是含有表达CD30的肿瘤细胞且在病理上有许多相似之处的淋巴瘤。ALCL通常在晚期被诊断出来,而cHL更常表现为局限性疾病。本研究的目的是阐明ALCL和cHL临床表现不同的潜在机制。除了已知cHL的霍奇金和里德-斯腾伯格(HRS)细胞中趋化因子CCL17和CCL22的过表达外,原发性ALCL和cHL病例中的趋化因子和趋化因子受体表达相似。与这些趋化因子的过表达一致,原发性cHL病例比ALCL遇到的T细胞微环境明显更密集。除了与微环境相互作用的差异外,通过在胶原凝胶中进行延时显微镜观察和transwell迁移试验评估,cHL细胞系的内在细胞运动性比ALCL细胞系更低且效率更低。因此,我们提出,与ALCL的肿瘤细胞相比,基础细胞运动性受损以及与微环境相互作用的差异共同阻碍了cHL中HRS细胞的扩散。